Clinical outcomes of phenotype-guided treatment in group D carbapenemase-producing Enterobacterales bacteremia
ABSTRACT International guidance recommends ceftazidime-avibactam for OXA-48-type carbapenemase-producing Enterobacterales (OXA-48-CPE) infections. However, OXA-48-CPE lacking extended spectrum and AmpC β-lactamases may remain susceptible to third-generation cephalosporins (3GC), potentially allowing...
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American Society for Microbiology
2025-07-01
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| Series: | Microbiology Spectrum |
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| Online Access: | https://journals.asm.org/doi/10.1128/spectrum.00273-25 |
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| author | Jinghao Nicholas Ngiam Matthew Chung Yi Koh Nicholas Jian Hao Chan Jeanette Teo Ka Lip Chew |
| author_facet | Jinghao Nicholas Ngiam Matthew Chung Yi Koh Nicholas Jian Hao Chan Jeanette Teo Ka Lip Chew |
| author_sort | Jinghao Nicholas Ngiam |
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| description | ABSTRACT International guidance recommends ceftazidime-avibactam for OXA-48-type carbapenemase-producing Enterobacterales (OXA-48-CPE) infections. However, OXA-48-CPE lacking extended spectrum and AmpC β-lactamases may remain susceptible to third-generation cephalosporins (3GC), potentially allowing treatment without avibactam. OXA-23 also has variable hydrolytic activity against 3GC. This study reviewed the outcomes of OXA-CPE bloodstream infections treated based on phenotypic susceptibility testing. A retrospective review of OXA-48-CPE and OXA-23-CPE bloodstream infections was conducted from February 2022 to July 2024. Data on antimicrobial susceptibility, patient background, infection source, treatments, and outcomes were analyzed. Whole-genome sequencing (WGS) determined the presence of β-lactamase genes in available isolates. Ten bloodstream infection episodes occurred in nine patients (eight OXA-48-like Escherichia coli [n = 4], Klebsiella pneumoniae [n = 4], and one OXA-23-CPE Proteus mirabilis), with a urinary source in 44.4% (n = 4). Of the isolates, 5/9 (55.5%) were 3GC-susceptible. WGS did not identify any extended-spectrum β-lactamases in these isolates. Three 3GC-susceptible cases (two OXA-48 and one OXA-23) were successfully treated with ceftriaxone. Among the 3GC-resistant cases, two were treated with ceftazidime-avibactam, and two with high-dose meropenem alone or in combination with aztreonam. One recurrence was observed in a case treated with ceftazidime-avibactam. Mortality was low, with one death reported in a patient treated with ceftazidime-avibactam. In this small study, 55.5% of OXA-48-CPE and OXA-23-CPE isolates retained 3GC susceptibility. When used for therapy, 3GC and non-β-lactam antibiotics demonstrated clinical efficacy where antibiotic susceptibility was demonstrated.IMPORTANCEThe Infectious Diseases Society of America guidance document recommends the use of ceftazidime-avibactam for the treatment of OXA-48-type carbapenemase-producing Enterobacterales (OXA-48-CPE). However, this antibiotic is expensive and not always available in some settings. The clinical outcomes of OXA-48-CPE and OXA-23-CPE bloodstream infections when treated with third-generation cephalosporin (3GC) remain unclear. Among 10 episodes in nine patients, we found that five isolates (55.5%) were 3GC-susceptible, with three cases successfully treated with ceftriaxone. Whole-genome sequencing demonstrated the absence of extended-spectrum β-lactamases in the 3GC-susceptible isolates, which aligns with phenotypic 3GC susceptibility. Mortality was low (1/9). Many OXA-48-CPE and OXA-23-CPE infections retain 3GC susceptibility, raising the possibility that these agents may be viable alternatives to ceftazidime-avibactam in select cases. |
| format | Article |
| id | doaj-art-de83cd5de8e14e978011c3e475d3fc94 |
| institution | OA Journals |
| issn | 2165-0497 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | American Society for Microbiology |
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| series | Microbiology Spectrum |
| spelling | doaj-art-de83cd5de8e14e978011c3e475d3fc942025-08-20T02:38:02ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972025-07-0113710.1128/spectrum.00273-25Clinical outcomes of phenotype-guided treatment in group D carbapenemase-producing Enterobacterales bacteremiaJinghao Nicholas Ngiam0Matthew Chung Yi Koh1Nicholas Jian Hao Chan2Jeanette Teo3Ka Lip Chew4Division of Infectious Diseases, Department of Medicine, National University Health System, Singapore, SingaporeDivision of Infectious Diseases, Department of Medicine, National University Health System, Singapore, SingaporeDivision of Infectious Diseases, Department of Medicine, National University Health System, Singapore, SingaporeDepartment of Laboratory Medicine, National University Hospital, Singapore, SingaporeDepartment of Laboratory Medicine, National University Hospital, Singapore, SingaporeABSTRACT International guidance recommends ceftazidime-avibactam for OXA-48-type carbapenemase-producing Enterobacterales (OXA-48-CPE) infections. However, OXA-48-CPE lacking extended spectrum and AmpC β-lactamases may remain susceptible to third-generation cephalosporins (3GC), potentially allowing treatment without avibactam. OXA-23 also has variable hydrolytic activity against 3GC. This study reviewed the outcomes of OXA-CPE bloodstream infections treated based on phenotypic susceptibility testing. A retrospective review of OXA-48-CPE and OXA-23-CPE bloodstream infections was conducted from February 2022 to July 2024. Data on antimicrobial susceptibility, patient background, infection source, treatments, and outcomes were analyzed. Whole-genome sequencing (WGS) determined the presence of β-lactamase genes in available isolates. Ten bloodstream infection episodes occurred in nine patients (eight OXA-48-like Escherichia coli [n = 4], Klebsiella pneumoniae [n = 4], and one OXA-23-CPE Proteus mirabilis), with a urinary source in 44.4% (n = 4). Of the isolates, 5/9 (55.5%) were 3GC-susceptible. WGS did not identify any extended-spectrum β-lactamases in these isolates. Three 3GC-susceptible cases (two OXA-48 and one OXA-23) were successfully treated with ceftriaxone. Among the 3GC-resistant cases, two were treated with ceftazidime-avibactam, and two with high-dose meropenem alone or in combination with aztreonam. One recurrence was observed in a case treated with ceftazidime-avibactam. Mortality was low, with one death reported in a patient treated with ceftazidime-avibactam. In this small study, 55.5% of OXA-48-CPE and OXA-23-CPE isolates retained 3GC susceptibility. When used for therapy, 3GC and non-β-lactam antibiotics demonstrated clinical efficacy where antibiotic susceptibility was demonstrated.IMPORTANCEThe Infectious Diseases Society of America guidance document recommends the use of ceftazidime-avibactam for the treatment of OXA-48-type carbapenemase-producing Enterobacterales (OXA-48-CPE). However, this antibiotic is expensive and not always available in some settings. The clinical outcomes of OXA-48-CPE and OXA-23-CPE bloodstream infections when treated with third-generation cephalosporin (3GC) remain unclear. Among 10 episodes in nine patients, we found that five isolates (55.5%) were 3GC-susceptible, with three cases successfully treated with ceftriaxone. Whole-genome sequencing demonstrated the absence of extended-spectrum β-lactamases in the 3GC-susceptible isolates, which aligns with phenotypic 3GC susceptibility. Mortality was low (1/9). Many OXA-48-CPE and OXA-23-CPE infections retain 3GC susceptibility, raising the possibility that these agents may be viable alternatives to ceftazidime-avibactam in select cases.https://journals.asm.org/doi/10.1128/spectrum.00273-25OXA-48carbapenemasecarbapenem-resistantEnterobacteralesoutcomesantibiotic choice |
| spellingShingle | Jinghao Nicholas Ngiam Matthew Chung Yi Koh Nicholas Jian Hao Chan Jeanette Teo Ka Lip Chew Clinical outcomes of phenotype-guided treatment in group D carbapenemase-producing Enterobacterales bacteremia Microbiology Spectrum OXA-48 carbapenemase carbapenem-resistant Enterobacterales outcomes antibiotic choice |
| title | Clinical outcomes of phenotype-guided treatment in group D carbapenemase-producing Enterobacterales bacteremia |
| title_full | Clinical outcomes of phenotype-guided treatment in group D carbapenemase-producing Enterobacterales bacteremia |
| title_fullStr | Clinical outcomes of phenotype-guided treatment in group D carbapenemase-producing Enterobacterales bacteremia |
| title_full_unstemmed | Clinical outcomes of phenotype-guided treatment in group D carbapenemase-producing Enterobacterales bacteremia |
| title_short | Clinical outcomes of phenotype-guided treatment in group D carbapenemase-producing Enterobacterales bacteremia |
| title_sort | clinical outcomes of phenotype guided treatment in group d carbapenemase producing enterobacterales bacteremia |
| topic | OXA-48 carbapenemase carbapenem-resistant Enterobacterales outcomes antibiotic choice |
| url | https://journals.asm.org/doi/10.1128/spectrum.00273-25 |
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